A gamma34.5 mutant of herpes simplex 1 causes severe inflammation in the brain.

A number of viral vectors are currently being evaluated as potential gene therapy vectors for gene delivery to the brain. As well as evaluating their ability to express a transgene for extended periods of time it is also essential to examine any cytotoxic immune response to such vectors as this may...

Full description

Bibliographic Details
Main Authors: McMenamin, M, Byrnes, A, Charlton, H, Coffin, R, Latchman, D, Wood, M
Format: Journal article
Language:English
Published: 1998
_version_ 1826298525017702400
author McMenamin, M
Byrnes, A
Charlton, H
Coffin, R
Latchman, D
Wood, M
author_facet McMenamin, M
Byrnes, A
Charlton, H
Coffin, R
Latchman, D
Wood, M
author_sort McMenamin, M
collection OXFORD
description A number of viral vectors are currently being evaluated as potential gene therapy vectors for gene delivery to the brain. As well as evaluating their ability to express a transgene for extended periods of time it is also essential to examine any cytotoxic immune response to such vectors as this may not only limit transgene expression but also cause irreparable harm. This work describes the effect of inoculating a gamma34.5 mutant of herpes simplex type 1 (1716lacZ) into the brain of different strains of rats and mice. Animals were monitored for weight loss and signs of illness, and their brains were evaluated for inflammation, beta-galactosidase expression and recoverable infectious virus. We report that there is (i) a powerful immune response consisting of an early non-specific phase and a later presumably T-cell-mediated phase; (ii) significant weight loss in some animals strains accompanied by severe signs of clinical illness and (iii) transient reporter gene expression in all animal strains examined. To be useful for gene therapy we suggest this virus requires further modification, it should be tested in several animal strains and the dose of virus used may be critical in order to limit damage.
first_indexed 2024-03-07T04:48:11Z
format Journal article
id oxford-uuid:d4099a70-d27d-4d44-b806-96e7fda8e64d
institution University of Oxford
language English
last_indexed 2024-03-07T04:48:11Z
publishDate 1998
record_format dspace
spelling oxford-uuid:d4099a70-d27d-4d44-b806-96e7fda8e64d2022-03-27T08:15:34ZA gamma34.5 mutant of herpes simplex 1 causes severe inflammation in the brain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d4099a70-d27d-4d44-b806-96e7fda8e64dEnglishSymplectic Elements at Oxford1998McMenamin, MByrnes, ACharlton, HCoffin, RLatchman, DWood, MA number of viral vectors are currently being evaluated as potential gene therapy vectors for gene delivery to the brain. As well as evaluating their ability to express a transgene for extended periods of time it is also essential to examine any cytotoxic immune response to such vectors as this may not only limit transgene expression but also cause irreparable harm. This work describes the effect of inoculating a gamma34.5 mutant of herpes simplex type 1 (1716lacZ) into the brain of different strains of rats and mice. Animals were monitored for weight loss and signs of illness, and their brains were evaluated for inflammation, beta-galactosidase expression and recoverable infectious virus. We report that there is (i) a powerful immune response consisting of an early non-specific phase and a later presumably T-cell-mediated phase; (ii) significant weight loss in some animals strains accompanied by severe signs of clinical illness and (iii) transient reporter gene expression in all animal strains examined. To be useful for gene therapy we suggest this virus requires further modification, it should be tested in several animal strains and the dose of virus used may be critical in order to limit damage.
spellingShingle McMenamin, M
Byrnes, A
Charlton, H
Coffin, R
Latchman, D
Wood, M
A gamma34.5 mutant of herpes simplex 1 causes severe inflammation in the brain.
title A gamma34.5 mutant of herpes simplex 1 causes severe inflammation in the brain.
title_full A gamma34.5 mutant of herpes simplex 1 causes severe inflammation in the brain.
title_fullStr A gamma34.5 mutant of herpes simplex 1 causes severe inflammation in the brain.
title_full_unstemmed A gamma34.5 mutant of herpes simplex 1 causes severe inflammation in the brain.
title_short A gamma34.5 mutant of herpes simplex 1 causes severe inflammation in the brain.
title_sort gamma34 5 mutant of herpes simplex 1 causes severe inflammation in the brain
work_keys_str_mv AT mcmenaminm agamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT byrnesa agamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT charltonh agamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT coffinr agamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT latchmand agamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT woodm agamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT mcmenaminm gamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT byrnesa gamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT charltonh gamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT coffinr gamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT latchmand gamma345mutantofherpessimplex1causessevereinflammationinthebrain
AT woodm gamma345mutantofherpessimplex1causessevereinflammationinthebrain